PMID: 

Lancet Infect Dis. 2009 Dec ;9(12):784-8. Epub 2009 Oct 30. PMID: 19879807

Abstract Title: 

Yearly influenza vaccinations: a double-edged sword?

Abstract: 

Yearly vaccination against seasonal influenza viruses is recommended for certain individuals at high risk of complications associated with influenza. It has been recommended in some countries, including the USA, that all children aged 6-59 months are vaccinated against seasonal influenza. However, it has been shown-mainly in animals-that infection with influenza A viruses can induce protective immunity to influenza A viruses of other unrelated subtypes. This so-called heterosubtypic immunity does not provide full protection, but can limit virus replication and reduce morbidity and mortality of the host. This type of immunity might be relevant to human beings when a new subtype of influenza A virus is introduced into the population, such as the new influenza A H1N1 virus responsible for the present influenza pandemic and the highly pathogenic avian influenza H5N1 viruses that are causing an ever increasing number of human infections with high mortality rates. Preventing infection with seasonal influenza viruses by vaccination might prevent the induction of heterosubtypic immunity to pandemic strains, which might be a disadvantage to immunologically naive people-eg, infants.

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PMID: 

Pediatr Dermatol. 2005 Mar-Apr;22(2):130-2. PMID: 15804301

Abstract Title: 

Vaccine-associated"wild-type"measles.

Abstract: 

Measles is the most contagious of the childhood exanthems and is the leading cause of vaccine-preventable deaths in children, mostly in developing countries. The prodromal stage, consisting of high fever and the triad of cough, coryza, and conjunctivitis, is followed by a caudal progressing rash over a period of 2 to 3 days. With a worldwide vaccination program in place, mortality and morbidity have decreased substantially. Receipt of the live attenuated vaccine generally causes no or only mild side effects such as a low-grade fever and a subtle rash. We report a 1-year-old boy who, 10 days after vaccination, developed vaccine measles which was clinically indistinguishable from the natural disease. Vaccine virus was detected by polymerase chain reaction in the patient's nasopharyngeal secretions.

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PMID: 

Clin Appl Thromb Hemost. 2018 Jan ;24(1):5-12. Epub 2016 Oct 21. PMID: 28301903

Abstract Title: 

Characterizing the Severe Reactions of Parenteral Vitamin K1.

Abstract: 

Parenteral vitamin K1 (phytonadione) is used for anticoagulant reversal, and a boxed warning exists with intravenous and intramuscular administration due to the possibility of severe reactions, including fatalities. These reactions resemble hypersensitivity or anaphylaxis, including anaphylactoid reaction, and have led to shock and cardiac and/or respiratory arrest. The objective of this review is to summarize the available literature detailing the anaphylactic/anaphylactoid reactions with parenteral vitamin K1 in order to better characterize the reaction and provide a more in-depth understanding of its importance. A comprehensive literature search of MEDLINE (1946 to June 2016) and EMBASE (1947 to June 2016) was conducted using the terms vitamin K1, phytonadione, phytomenadione, vitamin K group, anaphylaxis, polyoxyethylated castor oil, and cremophor. A total of 2 retrospective surveillance studies, 2 retrospective cohort studies, and 17 case reports were identified for inclusion and assessment. Based on a review of the literature, use of parenteral vitamin K1 may result in severe hypotension, bradycardia or tachycardia, dyspnea, bronchospasm, cardiac arrest, and death. These reactions are most consistent with a nonimmune-mediated anaphylactoid mechanism. It appears that intravenous administration is more frequently associated with these reactions and occurs at an incidence of 3 per 10 000 doses of intravenous vitamin K1. The solubilizer may also increase the risk of adverse reactions, which occurred in patients with and without previous exposure to vitamin K1. Although there are known factors that increase the risk of an adverse drug event occurring, reactions have been reported despite all precautions being properly followed.

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PMID: 

J Investig Allergol Clin Immunol. 2011 ;21(5):389-93. PMID: 21905502

Abstract Title: 

Autoimmunity and hepatitis A vaccine in children.

Abstract: 

BACKGROUND: Universal vaccination remains the most effective way of preventing the spread of many infectious diseases. Although most adverse effects attributed to vaccines are mild, rare reactions such as autoimmunity do occur.OBJECTIVES: We aimed to evaluate the possible role played by hepatitis A vaccine (HAV) in inducing the synthesis of autoantibodies. The study included 40 healthy children vaccinated with 2 doses of HAV at a 6-month interval. The children were investigated for autoantibodies including anti-nuclear antibodies (ANAs), anti-smooth muscle antibodies, anti-nDNA, anti-microsomal antibodies, anti-cardiolipin (aCL) immunoglobulin (Ig) M/IgG, anti-ds DNA, ANA profile, and anti-neutrophil cytoplasmic antibody profile.RESULTS: One month after the first dose, ANAs at a titer of 1:100 and aCL IgG at 23.7 IgM phospholipid units were detected in 4 children and 1 child, respectively. Of the ANA-positive children, 1 also had ASMA positivity, and another had perinuclear and cytoplasmic ANCA positivity. After the second dose, 3 of the children had aCL IgM. In addition, 2 distinct children had positive anti-thyroid microsomal antibodies and ANA after the second dose. The presence of these autoantibodies following vaccination was statistically significant (P = .002). At month 12 of the study, only 2 children continued to be ANA-positive at the same titer as after the first vaccine dose.CONCLUSIONS: Although HAV can induce the production of autoantibodies, none of the children developed autoimmune disorders. Long-term follow up is necessary to check whether autoimmune disorders develop in children who still have ANA. Genetic, immunological, environmental, and hormonal factors are also important in the development of vaccine-induced autoimmunity.

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PMID: 

J Matern Fetal Neonatal Med. 2014 Jul ;27(11):1180-1. Epub 2013 Oct 17. PMID: 24059412

Abstract Title: 

Anaphylactic shock due to vitamin K in a newborn and review of literature.

Abstract: 

Newborn infants are born with an immature innate immunity. They are less likely to develop anaphylaxis since their immune system is weaker than older infants and children. There are only a few reports of side effects after vitamin K injection in neonates although prophylaxis against hemorrhagic disease of the newborn with this drug has been in routine practice in all over the world for many years. We herein report a case of anaphylactic shock developing after the intramuscular administration of vitamin K1 in a newborn. To our knowledge, this patient is the first case of neonatal anaphylactic shock developing due to intramuscular administration of vitamin K1. We suggest the clinicians should be aware of this possibility of potentially fatal adverse effect occurring with intramuscular administration of vitamin K1.

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PMID: 

Metab Brain Dis. 2016 08 ;31(4):727-35. Epub 2016 Mar 8. PMID: 26956130

Abstract Title: 

Association of methylenetetrahydrofolate reductase (MTHFR) gene C677T polymorphism with autism: evidence of genetic susceptibility.

Abstract: 

Autism (MIM 209850) is a heterogeneous neurodevelopmental disease that manifests within the first 3 years of life. Numerous articles reported that dysfunctional folate-methionine pathway enzymes may play an important role in the pathophysiology of autism. Methylenetetrahydrofolate reductase (MTHFR) is a critical enzyme of this pathway and MTHFR C677T polymorphism reported as risk factor for autism in several case control studies. However, controversial reports were also published. Hence the present meta-analysis was designed to investigate the relationship of the MTHFR C677T polymorphism with the risk of autism. Electronic databases were searched for case control studies with following search terms – 'MTHFR', 'C677T', in combination with 'Autism'. Pooled OR with its corresponding 95 % CI was calculated and used as association measure to investigate the association between MTHFR C677T polymorphism and risk of autism. Total of thirteen studies were found suitable for the inclusion inthe present meta-analysis, which comprises 1978 cases and 7257 controls. Meta-analysis using all four genetic models showed significant association between C677T polymorphism and autism (ORTvs.C = 1.48; 95 % CI: 1.18-1.86; P = 0.0007; ORTT + CT vs. CC = 1.70, 95 % CI = 0.96-2.9, p = 0.05; ORTT vs. CC = 1.84, 95 % CI = 1.12-3.02, p = 0.02; ORCT vs.CC = 1.60, 95 % CI = 1.2-2.1, p = 0.003; ORTT vs.CT+CC = 1.5, 95 % CI = 1.02-2.2, p = 0.03). In total 13 studies, 9 studies were from Caucasian population and 4 studies were from Asian population. The association between C677T polymorphism and autism was significant in Caucasian (ORTvs.C = 1.43; 95 % CI = 1.1-1.87; p = 0.009) and Asian population (ORTvs.C = 1.68; 95 % CI = 1.02-2.77; p = 0.04) using allele contrast model. In conclusion, present meta-analysis strongly suggested a significant association of the MTHFR C677T polymorphism with autism.

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PMID: 

Biochim Biophys Acta Gen Subj. 2019 Dec ;1863(12):129243. Epub 2018 Oct 29. PMID: 30385391

Abstract Title: 

Multiple low-level exposures: Hg interactions with co-occurring neurotoxic substances in early life.

Abstract: 

All chemical forms of Hg can affect neurodevelopment; however, low levels of organic Hg (methylmercury-MeHg and ethylmercury-EtHg in Thimerosal-containing vaccines, hereafter 'TCV') exposures during early life (pregnancy and lactation) co-occur with other environmental neurotoxic substances. These neurotoxicants may act in parallel, synergistically, or antagonistically to Hg. Nevertheless, the risks of neurotoxicity associated with multiple neuro-toxicants depend on type, time, combinations of exposure, and environmental and/or genetic-associated factors. Neurological developmental disorders, delays in cognition and behavioral outcomes associated with multiple exposures (which include Hg) may show transient or lasting outcomes depending on constitutional and/or environmental factors that can interact to neutralize, aggravate or attenuate these effects; often these studies are challenging to interpret. During pregnancy and lactation, fish-MeHg exposure is frequently confounded with the opposing effects of neuroactive nutrients (in fish) that lead to positive, negative, or no effects on neurobehavioral tests. In infancy, exposures to acute binary mixtures (TCV- EtHg and Al-adjuvants in infant immunizations) are associated with increased risks of tics and other developmental disorders. Despite the certitude that promulgates single environmental neurotoxicants, empirical comparisons of combined exposures indicate that Hg-related outcome is uneven. Hg in combination with other neurotoxic mixtures may elevate risks of neurotoxicity, but these risks arise in circumstances that are not yet predictable. Therefore, to achieve the goals of the Minamata treaty and to safeguard the health of children, low levels of mercury exposure (in any chemical form) needs to be further reduced whether the source is environmental (air- and food-borne) or iatrogenic (pediatric TCVs).

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PMID: 

Toxicol Lett. 2020 Jan ;318:86-91. Epub 2019 Oct 24. PMID: 31669099

Abstract Title: 

Proton pump inhibitors block iron absorption through direct regulation of hepcidin via the aryl hydrocarbon receptor-mediated pathway.

Abstract: 

Proton pump inhibitors (PPIs) have been used worldwide to treat gastrointestinal disorders. A recent study showed that long-term use of PPIs caused iron deficiency; however, it is unclear whether PPIs affect iron metabolism directly. We investigated the effect of PPIs on the peptide hepcidin, an important iron regulatory hormone. First, we used the FDA Adverse Event Reporting System database and analyzed the influence of PPIs. We found that PPIs, as well as H2 blockers, increased the odds ratio of iron-deficient anemia. Next, HepG2 cells were used to examine the action of PPIs and H2 blockers on hepcidin. PPIs augmented hepcidin expression, while H2 blockers did not. In fact, the PPI omeprazole increased hepcidin secretion, and omeprazole-induced hepcidin upregulation was inhibited by gene silencing or the pharmacological inhibition of the aryl hydrocarbon receptor. In mouse experiments, omeprazole also increased hepatic hepcidin mRNA expression and blood hepcidin levels. In mice treated with omeprazole, protein levels of duodenal and splenic ferroportin decreased. Taken together, PPIs directly affect iron metabolism by suppressing iron absorption through the inhibition of duodenal ferroportin via hepcidin upregulation. These findings provide a new insight into the molecular mechanism of PPI-induced iron deficiency.

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PMID: 

Methodist Debakey Cardiovasc J. 2019 Jul-Sep;15(3):214-219. PMID: 31687101

Abstract Title: 

Cardiovascular Risk of Proton Pump Inhibitors.

Abstract: 

Proton pump inhibitors (PPIs) are effective agents for the treatment of gastroesophageal reflux (GERD). However, these drugs have not been approved for long-term use. Now sold over the counter, these agents are being used chronically for GERD without medical supervision. The long-term use of PPIs may have significant adverse effects, in part mediated by their effect of accelerating vascular aging. Physicians should assist patients in tapering off their use of PPIs and replacing them with lifestyle modifications and/or other agents that have better long-term safety profiles.

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PMID: 

Medicine (Baltimore). 2019 Nov ;98(44):e17788. PMID: 31689852

Abstract Title: 

Proton pump inhibitors and hypomagnesemia: A meta-analysis of observational studies.

Abstract: 

BACKGROUND: Previous meta-analyses have suggested that there might be an association between the use of proton pump inhibitors (PPIs) and the development of hypomagnesemia, although the conclusions were no definitive.METHODS: To provide an update on this topic, we performed a meta-analysis of all observational studies that examined the association between the use of PPIs and the development of hypomagnesemia. A literature search was conducted in MEDLINE, Scopus and Cochrane Central Register of Controlled Trials (January 1970 to June 2018) to identify observational studies that examined the association between the use of PPIs and the incidence and prevalence of hypomagnesemia.STUDY ELIGIBILITY CRITERIA: In the absence of randomized controlled trials, we focused primarily on observational studies, including cross-sectional, case-control, retrospective, and prospective cohort studies. There was no limitation on sample size or study duration. Random-effect models meta-analyses were used to compute pooled unadjusted and adjusted odds ratios (ORs) for binary variables.RESULTS: Sixteen observational studies were identified, including 13 cross-sectional studies, 2 case-control studies, and 1 cohort study, with a total of 131,507 patients. The pooled percentage of PPI users was 43.6% (95% confidence interval [CI] 25.0%, 64.0%). Among PPI users, 19.4% (95% CI 13.8%, 26.5%) had hypomagnesemia compared to 13.5% (95% CI 7.9%, 22.2%) among nonusers. By meta-analysis, PPI use was significantly associated with hypomagnesemia, with a pooled unadjusted OR of 1.83 (95% CI 1.26, 2.67; P = .002) and a pooled adjusted OR of 1.71 (95% CI 1.33, 2.19; P 

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